Siblings: Possibly Pesky, but May Protect Against JIA

Findings support the hygiene hypothesis for juvenile idiopathic arthritis.

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Children whose early childhood is spent in a home with siblings, which serves as a marker for exposure to microbes early in life, were at lower risk of developing juvenile idiopathic arthritis.

Note that adjustment for additional factors such as socioeconomic status and co-sleeping with parents, siblings, or pets during the first year of life did not significantly influence the study findings.

Children whose early childhood is spent in a home with siblings, which serves as a marker for exposure to microbes early in life, were at lower risk of developing juvenile idiopathic arthritis (JIA), an Australian study found.

Compared with being an only child, living with any brothers or sisters during the preschool years was associated with decreased likelihood of JIA (adjusted OR 0.46, 95% CI 0.28-0.74, P=0.001), according to Justine A. Ellis, PhD, of the Murdoch Childrens Research Institute in Parkville, Victoria, and colleagues.

Moreover, having three or more siblings further lowered the risk (OR 0.25, 95% CI 0.13-0.48, P<0.001), the researchers reported online in Arthritis and Rheumatology.

"The 'hygiene hypothesis' suggests that early life microbial exposure might influence the developing immune system to confer protection against later immune diseases. We and others have previously found associations of asthma, allergy, and autoimmune diseases such as multiple sclerosis with markers of reduced early life microbial exposure," they wrote.

Current thinking holds that JIA is a result of an interplay between genetic and environmental factors. Because the environmental factors are more amenable to intervention, this has become an area of heightened interest.

Previous studies on early life exposures and JIA have provided limited evidence and were inconsistent in measures of sibling exposures.

The analysis included 302 cases and two sets of controls. One control group consisted of 676 children recruited from the Royal Children's Hospital in Melbourne, and the other was 341 community controls recruited from health centers and schools.

For each participant, the researchers collected information about multiple factors, including sex, gestational age, maternal age, and number of siblings. An additional assessment of sibling exposure was the calculation of sibling-years, "defined as the total amount of time a child had one sibling for a full year at the age of 6."

In the analysis of cumulative sibling-years, having one to three younger siblings by age 6 was associated with a decreased risk (OR 0.36, 95% CI 0.18-0.73, P=0.005) compared with the hospital control group and also when compared with the community control group (OR 0.25, 95% CI 0.10-0.67, P=0.005).

Having more than three younger siblings by age 6 further reduced the risk compared with hospital controls (0.48, 95% CI 0.28-0.83, P=0.008) and community controls (OR 0.42, 95% CI 0.19-0.93, P=0.033).

Adjustment for additional factors such as socioeconomic status and co-sleeping with parents, siblings, or pets during the first year of life did not significantly influence the study findings.

In the study, "a clear pattern of association emerged in which higher total cumulative sibling exposure by age 6 was associated with a reduction in JIA risk."

Infection has long been suspected as a potential trigger for JIA. Both Epstein-Barr virus and parvovirus B-19 have been associated with transient arthropathy, and one study found that recent infection with B19, as evidenced by the presence of IgM antibodies, was associated with progression to JIA.

But in two other studies, children with oligoarticular JIA had evidence of a lower frequency of past B19 infection, suggesting that although recent infection might increase the risk, past infection might be protective.

"One explanation might be that early life infection with B19 increases the capacity of the immune system to eliminate the virus in later childhood," Ellis and colleagues commented.

"Our data have shown that increased exposure to siblings, particularly younger siblings, confers protection against developing JIA. Our data are novel, in that exposure to younger siblings has not been specifically considered before," they concluded.

A strength of the study was the inclusion of two control groups, while limitations included the possibility of recall bias for gestational age, the smaller number of controls in the community group, and a lack of information about exposure to other children outside the home.

The study was supported by the Australian National Health and Medical Research Council, the Australian Research Council, Arthritis Australia, Rebecca L. Cooper Foundation, LEW Carty Charitable Fund, ANZ Medical Research and Technologies in Victoria, Lynne Quayle Charitable Trust, the Victorian State Government Operational Infrastructure Support Program, and the Murdoch Childrens Research Institute.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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